Experiences of caring for women with cervical cancer: A qualitative study among male partners in Dar es Salaam, Tanzania.

BACKGROUND: More than three-fourths of cervical cancer cases occur in low- and middle-income countries, with sub-Saharan Africa (SSA) accounting for approximately 25% of global mortality. The significant rise in the prevalence of cervical cancer in SSA amplifies the burden on caregivers, contributing to elevated rates of mental illness, particularly among spouses who provide care. Men who assume the role of caregivers for their partners with cervical cancer encounter unique challenges and substantial adjustments across multiple facets of life, impacting both their own quality of life and that of their partners. Despite this, there is a notable lack of extensive research on the experiences of male partners in caregiving roles, particularly within SSA countries like Tanzania. Therefore, this study aimed to explore the experiences of male partners providing care for women with cervical cancer in Dar es Salaam, Tanzania. METHODS: An exploratory qualitative study was undertaken to explore the experiences of 13 male partners, selected purposively and guided by the principle of saturation. Data gathering employed in-depth interviews utilizing a semistructured interview guide, with subsequent analysis conducted via a thematic analysis approach. RESULTS: Five themes and 13 subthemes were generated, encompassing psychosocial distress, attitudes towards cervical cancer, unity in the provision of care, economic burden, and altered sexual relationships. Participants reported experiencing emotional distress, shifts in social responsibilities, financial challenges, and unfulfilled sexual needs. Moreover, they expressed the need for social, psychological, financial, and sexual and reproductive support. CONCLUSION: This study underscores the numerous challenges encountered by male partners caring for women with cervical cancer, encompassing emotional distress, financial strain, and shifts in social and sexual dynamics. The identified themes and subthemes highlight the intricate interplay of these difficulties and stress the necessity for holistic support systems addressing the social, psychological, financial, and sexual aspects of male partners' experiences. The findings emphasize the importance of designing and implementing comprehensive support programmes tailored to the diverse needs of male partners, ultimately enhancing their quality of life and overall well-being. PATIENT OR PUBLIC CONTRIBUTION: Before the study, the nursing manager assisted in selecting three male partners randomly. These partners were involved in the design of the participants' information sheet, the evaluation of the interview schedule and rooms, and the dissemination of information about the study's purpose to the target population. Their valuable input contributed to improving the participant information sheet, refining data collection procedures and addressing ethical considerations. However, these individuals were not considered study participants. Throughout the study, in-charge nurses in the hospital were informed about the study's goals and helped organize appointments with participants and manage the interview schedule.

Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer.

BACKGROUND: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. RESULT: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.

Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid.

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.

Combining cisplatin with Pinellia pedatisecta Schott lipid-soluble extract induces tumor immunogenic cell death in cervical cancer.

BACKGROUND: Pinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PURPOSE: To explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. METHODS: Cervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. RESULTS: PE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. CONCLUSIONS: This study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Case report: Synchronous tumors of the female reproductive tract in systemic lupus erythematosus: report of two cases and review of the literature.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors. Case presentation: We report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer. Conclusion: The presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE.

Barriers to cervical cancer screening in Africa: a systematic review.

INTRODUCTION: Africa has one of the highest burdens of cervical cancer in the world. The unacceptably high incidence and mortality rates could be reduced through implementing a comprehensive approach to its prevention and control that includes screening, which however, is low in most low-and-middle-income countries. Hence, this systematic review aims at exploring factors that prevent women from utilising cervical cancer screening services in the region. METHODS: A mixed method systematic review was conducted. A search was performed on PubMed (Medline), EMBASE, CINAHL (EBSCOHOST) and Scopus databases for articles published until May 2019 without time, language or study design limits. Two reviewers critically appraised the included studies independently using the standard quality assessment criteria for evaluating primary research papers. Results of the quantitative and mixed methods studies were transformed into qualitative data and synthesised using thematic analysis. RESULTS: From a potential 2 365 studies, 24 from 11 countries met the eligibility criteria and were selected; eight qualitative, 13 quantitative, and three that used the mixed-method approach. The primary barriers were identified as poor access to screening services, lack of awareness and knowledge on cervical cancer and screening, and socio-cultural influences. Service providers perceived lack of skills, screening equipment and supplies, and staff shortages as the major barriers to the provision of screening services. CONCLUSION: Barriers to cervical cancer screening in Africa are multifaceted and require a holistic approach that will address them concurrently at the health system, individual, interpersonal, community and structural levels. Political will complimented by stakeholder involvement is required in the development and implementation of strategies that will ensure acceptability, availability, accessibility, and affordability of screening to minimise barriers in accessing the service.

Cervical Cancer Therapeutics: An In-depth Significance of Herbal and Chemical Approaches of Nanoparticles.

Cervical cancer emerges as a prominent health issue, demanding attention on a global level for women's well-being, which frequently calls for more specialized and efficient treatment alternatives. Traditional therapies may have limited tumour targeting and adverse side effects. Recent breakthroughs have induced a transformative shift in the strategies employed against cervical cancer. biocompatible herbal nanoparticles and metallic particles made of gold, silver, and iron have become promising friends in the effort to fight against this serious disease and understand the possibility of these nanoparticles for targeted medication administration. this review article delves into the latest advancements in cervical cancer research. The safety and fabrication of these nanomaterials and their remarkable efficacy against cervical tumour spots are addressed. This review study, in short, provides an extensive introduction to the fascinating field of metallic and herbal nanoparticles in cervical cancer treatment. The information that has been examined points to a bright future in which women with cervical cancer may experience fewer side effects, more effective therapy, and an improved quality of life. This review holds promise and has the potential to fundamentally reshape the future of cervical cancer treatment by addressing urgent issues and unmet needs in the field.

Investigation of in-vitro Anti-Cancer and Apoptotic Potential of Garlic-Derived Nanovesicles against Prostate and Cervical Cancer Cell Lines.

OBJECTIVE: Investigate the anti-cancerous potential of garlic-derived nanovesicles (GDNVs), exploring their cytotoxic effects on HeLa and PC-3 cell lines, and elucidate the underlying mechanisms, including apoptosis induction and inhibition of epithelial-mesenchymal transition (EMT). METHODS: GDNVs were isolated using differential centrifugation and ultracentrifugation. Characterization was performed through dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM), and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity assessments on HeLa and PC-3 cell lines using MTT assay. Apoptosis induction was evaluated through nuclear morphology changes and quantification of apoptotic cells using DAPI and PI/annexin V analysis. Western blot of apoptosis-related proteins (bcl-2, bax, caspase-3) was analysed. Anti-metastatic potential was assessed using wound healing assay and EMT transition inhibition. RESULTS: Garlic-derived nanovesicles (GDNVs), characterized by a size of 134.2 nm, demonstrated a substantial and dose- as well as time-dependent anti-proliferative impact on HeLa and PC-3 cell lines. The induction of apoptosis was unequivocally established through discernible modifications in nuclear morphology. The apoptotic cell count in HeLa and PC-3 cells increased by 42.4 ± 4.2% and 38.2 ± 3.2%, respectively. Comprehensive Western blot demonstrated alterations in the expression of key apoptotic regulators, namely bcl-2, bax, and caspase-3, providing robust evidence for the initiation of apoptosis. Furthermore, GDNVs exerted a significant inhibitory effect (p < 0.001) on the migratory potential of both HeLa and PC-3 cells. Moreover, there was a discernible association between GDNVs and the suppression of Epithelial-Mesenchymal Transition (EMT), emphasizing their role in impeding the metastatic potential of these cancer cell lines. CONCLUSION: This study establishes, for the first time, the anti-cancerous potential of GDNVs. The observed dose- and time-dependent anti-proliferative effects, selective cytotoxicity, apoptosis induction, and anti-migratory potential highlight GDNVs as a promising candidate for cancer treatment.

Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo.

Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention.

Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021.

BACKGROUND: In Japan, comprehensive cancer statistics data have been collected through national cancer registries, but these data are rarely summarized and reported in research articles. METHODS: Here, we compiled the national registry data on malignant tumors originating from gynecologic organs (ovary, corpus uteri, cervix uteri) in Japan. RESULTS: The number of new patients in 2019 was 13,380, 17,880, and 10,879, respectively, and the number of deaths in 2021 was 5081, 2741, and 2894, respectively. Compared with 40 years ago, the incidence of ovarian cancer has tripled, the incidence of uterine corpus cancer (mainly endometrial cancer) has increased eightfold, the mortality rate of uterine corpus cancer has tripled, and the incidence of cervical intraepithelial cancer has increased ninefold in data standardized by the world population. Compared with the United States, the incidence rate of ovarian cancer has overtaken and the mortality rate of uterine corpus cancer is the same, while both the incidence and mortality rates of cervical cancer are higher in Japan. CONCLUSION: The incidence of gynecologic cancer is increasing significantly in Japan.

Vitamin D and Its Receptors in Cervical Cancer.

Several studies have investigated the relationship between vitamin D (VD) and its receptors (VDR) and the risk of cervical cancer. However, the underlying mechanisms that underpin these associations remain incompletely comprehended. In this review, we analyzed the impacts of VD and VDR on cervical cancer and related mechanisms, and discussed the effects of VD, calcium, and other vitamins on cervical cancer. Our literature research found that VD, VDR and their related signaling pathways played indispensable roles in the occurrence and progression of cervical cancer. Epidemiological studies have established associations between VD, VDR, and cervical cancer susceptibility. Current studies have shown that the inhibitory effect of VD and VDR on cervical cancer may be attributed to a variety of molecules and pathways, such as the EAG potassium channel, HCCR-1, estrogen and its receptor, p53, pRb, TNF-α, the PI3K/Akt pathway, and the Wnt/ß-catenin pathway. This review also briefly discussed the association between VDR gene polymorphisms and cervical cancer, albeit a comprehensive elucidation of this relationship remains an ongoing research endeavor. Additionally, the potential ramifications of VD, calcium, and other vitamins on cervical cancer has been elucidated, yet further exploration into the precise mechanistic underpinnings of these potential effects is warranted. Therefore, we suggest that further studies should focus on explorations into the intricate interplay among diverse molecular pathways and entities, elucidation of the mechanistic underpinnings of VDR polymorphic loci changes in the context of HPV infection and VD, inquiries into the mechanisms of VD in conjunction with calcium and other vitamins, as well as investigations of the efficacy of VD supplementation or VDR agonists as part of cervical cancer treatment strategies in the clinical trials.

Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms.

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/ß-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

Sexual quality of life after gynaecological cancer: what young women want.

PURPOSE: Psychosexual distress is known to be a common complication of treatment for gynaecological cancer (GC), affecting the sexual quality of life (SQoL) for an increasing number of young gynaecological cancer survivors (YGCS). The SQoL in YGCS study aimed to identify strategies that are acceptable and helpful to YGCS in protecting and improving SQoL, using a salutogenic approach. METHODS: A qualitative study was undertaken with young women aged 18-45 and pre- or perimenopausal at diagnosis. Semi-structured interviews were conducted on Zoom and a thematic analysis of transcripts was completed in NVivo. RESULTS: Fifteen interviews with YGCS revealed three themes for strategy development: psychosexual education, psychosocial support, and healthcare policy and strategy to establish SQoL as standard care in gynaecologic oncology. CONCLUSION: The strategies put forward by YGCS showed the need for a holistic, patient-centric, and multidisciplinary approach to SQoL. A better understanding of the strategies acceptable to YGCS, including the importance of using a trauma-informed approach to communication and care, can help healthcare providers play a vital role in protecting and improving SQoL.

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway.

OBJECTIVE: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway. METHODS: Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC50) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. RESULTS: Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05). CONCLUSION: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

The impact of in-house pathology services on downstaging cervical cancer in Tanzania over an 18-year period.

PURPOSE: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. METHODS: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. RESULTS: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). CONCLUSIONS: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs.

Phytochemical profile and biological activities of Bromelia antiacantha extracts

Abstract Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Resumo Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Phytochemical profile and biological activities of Bromelia antiacantha extracts / Perfil fitoquímico e atividades biológicas de extratos de Bromelia antiacantha

Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Selenium promotes immunogenic radiotherapy against cervical cancer metastasis through evoking P53 activation.

Radiotherapy is still the recommended treatment for cervical cancer. However, radioresistance and radiation-induced side effects remain one of the biggest clinical problems. Selenium (Se) has been confirmed to exhibit radiation-enhancing effects for cancer treatment. However, Se species dominate the biological activities and which form of Se possesses better radiosensitizing properties and radiation safety remains elusive. Here, different Se species (the valence state of Se ranged from - 2, 0, +4 to + 6) synergy screen was carried out to identify the potential radiosensitizing effects and radiation safety of Se against cervical cancer. We found that the therapeutic effects varied with the changes in the Se valence state. Sodium selenite (+4) displayed strong cancer-killing effects but also possessed severe cytotoxicity. Sodium selenate (+6) neither enhanced the killing effects of X-ray nor possessed anticancer activity by its alone treatment. Although nano-selenium (0), especially Let-SeNPs, has better radiosensitizing activity, the - 2 organic Se, such as selenadiazole derivative SeD (-2) exhibited more potent anticancer effects and possessed a higher safe index. Overall, the selected Se drugs were able to synergize with X-ray to inhibit cell growth, clone formation, and cell migration by triggering G2/M phase arrest and apoptosis, and SeD (-2) was found to exhibit more potent enhancing capacity. Further mechanism studies showed that SeD mediated p53 pathway activation by inducing DNA damage through promoting ROS production. Additionally, SeD combined with X-ray therapy can induce an anti-tumor immune response in vivo. More importantly, SeD combined with X-ray significantly inhibited the liver metastasis of tumor cells and alleviated the side effects caused by radiation therapy in tumor-bearing mice. Taken together, this study demonstrates the radiosensitization and radiation safety effects of different Se species, which may shed light on the application of such Se-containing drugs serving as side effects-reducing agents for cervical cancer radiation treatment.

Exploration of the Mechanism of Kaempferol in the Treatment of Cervical Cancer-based on Metabolomics and Network Pharmacology.

BACKGROUND: Cervical cancer is a prevalent malignancy among women globally. OBJECTIVE: We aimed to uncover the mechanism of action of kaempferol in the treatment of cervical cancer using an integrated approach that combines metabolomics with network pharmacology. METHODS: Initially, we investigated the specific metabolites and potential pathways influenced by kaempferol in the pathological progression of cervical cancer, employing UHPLC-Q-Orbitrap MS metabolomics. In addition, network pharmacology analysis was performed to ascertain the pivotal targets of kaempferol in the context of CC therapy. RESULTS: Metabolomics analysis indicated that the therapeutic effect of kaempferol on cervical cancer is primarily associated with 11 differential metabolites and 7 metabolite pathways. These pathways include arginine and proline metabolism, the tricarboxylic acid cycle, phenylalanine, tyrosine, and tryptophan biosynthesis, fatty acid biosynthesis, glycerophospholipid metabolism, pantothenate and CoA biosynthesis, and tyrosine metabolism. Additionally, kaempferol was found to regulate 3 differential metabolites, namely palmitic acid, citric acid, and L-tyrosine, by directly targeting 7 specific proteins, including AKR1B1, CS, EGFR, PLA2G1B, PPARG, SLCO2B1, and SRC. Furthermore, molecular docking demonstrated strong binding affinities between kaempferol and 7 crucial targets. CONCLUSION: This study elucidates the intricate mechanisms by which kaempferol acts against cervical cancer. Furthermore, this research offers a novel approach to investigating the potential pharmacological mechanisms of action exhibited by natural compounds.